Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria
Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria
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DOI：
10.1073/pnas.1500107112
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发表时间：
2015-06-09
影响因子：
11.1
通讯作者：
Qimron, Udi
中科院分区：
文献类型：
--
作者：
Yosef, Ido;Manor, Miriam;Qimron, Udi
病原体对抗生素耐药性的威胁日益增加，需要开发新的抗菌策略。在这里，我们提出了一个遗传策略的概念证明，旨在使细菌对抗生素敏感，并选择性地杀死耐药细菌。我们使用温和的引物将功能性成簇的规则间隔短回文重复序列（CRISPR）-CRISPR相关（Cas）系统递送到耐药性细菌的基因组中。所递送的CRISPR-Cas系统破坏赋予抗生素抗性的质粒和遗传修饰的裂解酶。抗生素致敏和保护免受溶菌性肺炎之间的这种联系是该策略的关键特征。它允许编程的溶解性细菌，以杀死只有抗生素耐药的细菌，同时保护抗生素致敏的细菌。根据这一策略设计的噬菌体可用于医院表面和洗手液，以促进用敏感的病原体替换耐药病原体。
The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.